The long-range research goals of this laboratory are to understand the genetic events that accompany lymphocyte differentiation and that specify lymphocyte function. One focus of our current studies is the mechanism by which the immunoglobulin heavy chain (IgH) intron and 3' enhancers control Ig gene expression in developing B lymphocytes. In particular, the hypothesis that these enhancers operate at separate stages in B cell development is being tested. Another focus of this laboratory's research is the cell-type specificity of Ig gene expression. We have shown that non-B cells, in particular a T lymphoma representing the other major subtype of lymphocyte, possess a factor(s) capable of silencing the IgH locus. This gene-extinguishing activity presumably is responsible for maintaining this locus in an inactive state within T lineage cells. We are using several strategies to both biochemically characterize and genetically clone the factor(s) responsible for Ig gene silencing in non- B cells. We have begun related studies that allow us to more broadly consider the transcriptional controls distinguishing the genetic programs of B and T lymphocytes, and have found evidence for a common regulator of a family of B cell-specific genes. MBRS students will participate in these studies, first by learning a wide range of research techniques (tissue culture; DNA analysis; assays of gene expression; cell fusion) from more senior lab members. After this training period, students will be given a defined project that falls within the aims of the research described above, and will be encouraged to work and think independently to accomplish the defined goal. In addition to laboratory work, students will participate in laboratory meetings in which both they and other lab members present and discuss their work. The goal is to help the students achieve tangible research goals as they are being trained to function as research scientists.